The present study was carried on to determine the effects of Citrus limon peel essential oil as feed supplement on non-specific immune system, disease resistance against Edwardsiella tarda and growth performance in Mozambique tilapia (Oreochromis mossambicus). Fish were randomly distributed at 25 fish per 50 L aquariums and fed with commercial diets supplemented with different ratios (0% for the control group and then 0.5%, 0.75% and 1%) of limon essential oil for 60 days. At the end of the feeding trial, immunological, biochemical and biometrical parameters were assessed. Also following 60 days of feeding, the fish were injected with E. tarda and mortalities were recorded. Results showed that C. limon peel essential oil supplementation diet enhanced the Nitro blue tetrazolium (NBT) positive cell count and total white blood cell (WBC) in tilapia. At the same time a significant change was found in the lysozyme activity and myeloperoxidase activity in serum. Serum glucose, cholesterol and triglycerides decreased while total protein increased in the groups fed with C. limon essential oil supplemented diets. All C. limon peel essential oil supplemented groups showed reduced mortalities following E. tarda infection compared with the control group. The results indicated that C. limon peel essential oil supplementation could improve non-specific immune parameters and growth performance and decrease mortality rate of cultured tilapia.